Objectives: Granular corneal dystrophies (GCD) are characterized by small, discrete, sharp-edged, grayish-white opacities in the corneal stroma. Among the genes responsible for the development of GCD, the most strongly related gene is transforming growth factor beta-induced (TGFBI), located in the 5q31.1 locus. Studies show that R124H in exon 4 and R555W in exon 12 are hot-spot mutations in the TGFBI gene that lead to GCD development. In this study, we aimed to investigate these two hot-spot mutations in exons 4 and 12 of the TGFBI gene and other possible mutations in the same regions, which code important functional regions of the protein, in Turkish families with GCD and to determine the relationship between the mutations and disease and related phenotypes.
Materials and methods: The study included 16 individuals diagnosed with GCD type 1 (GCD1), 11 of these patients' healthy relatives, and 28 unrelated healthy individuals. DNA was obtained from peripheral blood samples taken from each individual and polymerase chain reaction was used to amplify target gene regions. Genotyping studies were done by sequence analysis.
Results: The R124S mutation in exon 4 of TGFBI was not detected in the patients or healthy individuals in our study. However, all individuals diagnosed as having GCD1 were found to be heterozygous carriers of the R555W mutation in exon 12 of TGFBI. This mutation was not detected in healthy family members or control individuals unrelated to these families. In addition, we detected the silent mutation F540F in exon 12 and c.32924 G>A substitution in an intronic region of the gene in a few patients and healthy individuals.
Conclusion: Our study strongly supports the association of GCD1 with R555W mutation in exon 12 region of the TGFBI gene, as reported in the literature.
Keywords: Granular corneal dystrophy type 1; R555W mutation; TGFBI gene.